Optimising the ECMO treatment regimen increases the survival rate for adult patients with acute fulminant myocarditis: A single-centre retrospective cohort study.

Background: Applying Extracorporeal membrane oxygenation (ECMO) to patients with acute fulminant myocarditis (AFM) reduces their mortality. The survival rate is 55.6-71.9% for adult AFM patients, which is lower than that for paediatric patients (63-81%). In our centre, the survival rate of ECMO for adult patients with AFM was 66.7% from January 2003 to 2012. In January 2013, the therapeutic regimen was optimised, and then the survival rate increased to 89.1% by January 2022. This article analyses the reasons for the improved survival rate following the optimisation of treatment protocols. Methods: The data for adult patients with AFM who underwent ECMO for a poor response conventional treatment from January 2003 to January 2022 were reviewed. According to different treatment regimens, the AFM patients were divided into an old and a new regimen group. Univariate and multivariate logistic regression analyses were performed on the data before and after ECMO. Results: Fifty-five patients were enrolled in the age (31.2 ± 11.3), including 24 males. Forty-nine patients were weaned successfully from ECMO [duration: (4.1 ± 1.8) d], all of whom were discharged from the hospital, with a survival rate of 89.1%. Compared with the old regimen group, the new regimen group had a shorter duration of shock to ECMO, a lower proportion of patients receiving extracorporeal cardiopulmonary resuscitation (ECPR), a lower Vasoactive Inotropic Score (VIS), and lower levels of lactic acid, and high-sensitivity troponin T before ECMO (p < 0.05). Compared with the old regimen group, after ECMO, the new regimen group had lower ECMO flow, lower proportion of left ventricular dilation and lower limb ischemia injury, the duration of ECMO was shorter, and significantly improved the survival rate, the difference was statistically significant (P < 0.05). The duration of shock to ECMO and VIS before ECMO were independent risk factors for the survival rate (p < 0.05). Conclusion: Early ECMO initiation in adult AFM patients with a poor response to conventional therapy and low-flow ECMO to meet metabolic needs can reduce serious complications affecting the prognosis, may be associated with better outcomes.

Mediastinal Nodal Staging Performance of Combined Endobronchial and Esophageal Endosonography in Lung Cancer Cases: A Systematic Review and Meta-Analysis.

By searching lliteratures till January 5, 2022, we evaluated the role of the mediastinal nodal staging of endobronchial ultrasound-guided fine-needle aspiration (EBUS) and endoscopic ultrasound-guided fine-needle aspiration (EUS) in lung cancer. A total of 20 studies with 2,961 patients were included in this study. The pooled sensitivity, specificity, PLR, and NLR for EBUS were 0.79, 0.97, 27.29, and 0.25, respectively. EUS showed staging performance similar to EBUS. The staging performance was significantly improved when combining EBUS + EUS.

Site-selective modification of exendin 4 with variable molecular weight dextrans by oxime-ligation chemistry for improving type 2 diabetic treatment.

Dextrans, as natural and biocompatible polysaccharides, are a promising candidate as PEG alternatives to improve the therapeutic profiles of biotherapeuticals. In this work, we chemically mutated the lysine residue in native Ex4 to aminooxyl containing lysine (K*) and three Ex4 analogs (Ex4-12K*, Ex4-27K*, Ex4-12K*-27K*) were synthesized and site-selectively modified with variable Mw of dextrans by facile oxime-ligation chemistry. The biological activities of six dextran-Ex4 conjugates were studied by in vitro and in vivo experiment. It was demonstrated that dextranylation at the 12-site of Ex4 determined the in vitro potency as GLP-1R agonist and the in vivo acute glucose-lowering activity. Furthermore, the in vivo long-acting antidiabetic experiment demonstrated that hypoglycemic effect was strongly dependent on the dextranylation site of Ex4 as well as the size of dextran. And Dextran-Ex4-12K*(20,000) exhibited the best long acting hypoglycemic activity in STZ/HFD-induced T2D mice and is a promising once daily reagent for T2D treatment.

Site-specific C-terminal dinitrophenylation to reconstitute the antibody Fc functions for nanobodies.

Nanobodies are a class of camelid-derived single-domain antibodies that have many potential advantages over conventional antibodies and have been utilized to develop new therapeutic strategies for cancer and other diseases. However, nanobodies lack the Fc region of a conventional antibody, which possesses many functions, e.g., eliciting antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC), essential for effective immunotherapy. The small molecular size of nanobodies also leads to poor pharmacokinetics, such as short in vivo half-life. To address these deficiencies, an endogenous antibody-based strategy to reconstitute the Fc functions for nanobodies was developed. As a proof-of-principle, an anti-human EGFR nanobody, 7D12, was selected to conduct C-terminal modification with the dinitrophenyl (DNP) hapten through Sortase A-mediated site-specific ligation. It was expected that the DNP motif would recruit endogenous human anti-DNP antibodies to indirectly reinstate the Fc functions. The resultant nanobody-DNP conjugates were shown to exhibit specific and high affinity binding to human EGFR expressed on target cancer cells. It was further proved that in the presence of anti-DNP antibody, these conjugates could mediate potent ADCC and CDC in vitro and exhibit significantly elongated half-life in vivo. Ultimately, it was proven in severe combined immunodeficiency (SCID) mice that treatment with the nanobody 7D12-DNP conjugate and anti-DNP mouse serum could inhibit xenograft tumor growth efficiently. In view of the abundance of anti-DNP and other endogenous antibodies in the human blood system, this could be a generally applicable approach employed to reconstitute the Fc functions for nanobodies and develop nanobody-based cancer immunotherapy and other therapies.

Immobilization of Staphylococcus aureus Sortase A on Chitosan Particles and Its Applications in Peptide-to-Peptide Ligation and Peptide Cyclization.

Chitosan macro-particles prepared by the neutralization method were applied to Sortase A (SrtA) immobilization using glutaraldehyde as a crosslinking agent. The particles were characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM). Response surface methodology (RSM) was employed to optimize the immobilization process. An average specific activity of 3142 U (mg protein)-1 was obtained under optimized immobilization conditions (chitosan concentration 3%, SrtA concentration 0.5 mg·mL-1, glutaraldehyde concentration 0.5%, crosslinking and immobilization at 20 °C, crosslinking for 3 h, and an immobilization time of 8 h). The transpeptidase activity of immobilized SrtA was proved by a peptide-to-peptide ligation with a conversion yield approximately at 80%, and the immobilized catalyst was successfully reused for five cycles without obvious activity loss. Moreover, the scale-up capability of using immobilized SrtA to catalyze a head-to-tail peptide cyclization was investigated in a batch reaction and the conversion yield was more than 95% when using 20 mg of peptide as a substrate.

One-step purification and immobilization of extracellularly expressed sortase A by magnetic particles to develop a robust and recyclable biocatalyst.

Sortase A (SrtA) is a transpeptidase widely used to site-specifically modify peptides and proteins and shows promise for industrial applications. In this study, a novel strategy was developed for constructing immobilized-SrtA as a robust and recyclable enzyme via direct immobilization of extracellularly expressed SrtA in the fermentation supernatant using magnetic particles. Efficient extracellular SrtA expression was achieved in Escherichia coli through molecular engineering, including manipulation of the protein transport pathway, codon optimization, and co-expression of molecular chaperones to promote expressed SrtA secretion into the medium at high levels. Subsequently, a simple one-step protocol was established for the purification and immobilization of SrtA containing a His-tag from the fermentation supernatant onto a nickel-modified magnetic particle. The immobilized SrtA was proved to retain full enzymatic activity for peptide-to-peptide ligation and protein modification, and was successfully reused for five cycles without obvious activity loss.